Analysis of the mechanisms involved in the inflammatory response induced by des-Arg9-bradykinin in the rat pleural cavity

Pinheiro, Rafael Mota; Campos, Maria M.; Calixto, João Β.

doi:10.1007/pl00000235

Cited by 8 publications

(6 citation statements)

References 27 publications

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“…Blocking of both receptors also displayed cell adhesion molecule expression modulation, which supports the existence of alternative pathways for the regulation of endothelium-leukocyte adhesion interaction (47)(48)(49). Such regulation seems to be dependent on cytokines, LPS, or other mediators of inflammation independent of bradykinin B1 and B2 receptor pathways (49). Although angiogenesis is an important process in the development and perpetuation of rheumatoid arthritis, there was no difference among the disease-untreated and treated groups.…”

Section: Discussionmentioning

confidence: 65%

“…This hypothesis could be tested by use of a B1 receptor agonist; however, the response may be limited by the development of tachyphylaxis (45,46). Blocking of both receptors also displayed cell adhesion molecule expression modulation, which supports the existence of alternative pathways for the regulation of endothelium-leukocyte adhesion interaction (47)(48)(49). Such regulation seems to be dependent on cytokines, LPS, or other mediators of inflammation independent of bradykinin B1 and B2 receptor pathways (49).…”

Section: Discussionmentioning

confidence: 96%

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Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

et al. 2004

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Bradykinin (BK), a vasoactive, proinflammatory nonapeptide, promotes cell adhesion molecule (CAM) expression, leukocyte sequestration, inter-endothelial gap formation, and protein extravasation in postcapillary venules. These effects are mediated by bradykinin-1 (B1R) and-2 (B2R) receptors. We delineated some of the mechanisms by which BK could influence chronic inflammation by altering CAM expression on leukocytes, endothelium, and synovium in joint sections of peptidoglycan-polysaccharide-injected Lewis rats. Blocking B1R results in significantly increased joint inflammation. Immunohistochemistry of the B1R antagonist group revealed increased leukocyte and synovial CD11b and CD54 expression and increased CD11b and CD44 endothelial expression. B2R antagonism decreased leukocyte and synovial CD44 and CD54 and endothelial CD11b expression. Although these findings implicate B2R involvement in the acute phase of inflammation by facilitating leukocyte activation (CD11b), homing (CD44), and transmigration (CD54). Treatment with a B2R antagonist did not affect the disease evolution in this model. In contrast, when both BK receptors are blocked, the aggravation of inflammation by B1R blockade is neutralized and there is no difference from the disease-untreated model. Our findings suggest that B1R and B2R signaling show physiologic antagonism. B1R signaling suggests involvement in down-regulation of leukocyte activation, transmigration, and homing. Further studies are needed to evaluate the B1 receptor agonist's role in this model.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 96%

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

et al. 2004

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“…The use of ACEi has been associated with the occurrence of side effects such as AE [11,12]. Accumulation of kinins namely bradykinin (BK) or its metabolites has been suggested to be involved in these effects [12][13][14]. The knowledge of the in vivo profile of two dual ACE/NEP inhibitors, which are currently undergoing clinical trials in terms of kinins (bradykinin, BK1-8 and other metabolites) accumulation, should be of great interest.…”

Section: Discussionmentioning

confidence: 99%

“…However, their use in the clinic is limited because they have been associated with the occurrence of side effects such as AE [11,12]. The mechanism of AE remains unresolved, however, several studies performed in rats or in humans suggested that accumulation of BK and that of its metabolite BK1-8 in plasma may participate in the occurrence of AE [12][13][14]. Because it is important to have active but also safe compounds, a new class of cardiovascular drugs that simultaneously inhibit both ACE and NEP has been developed (for a review see ref [15]).…”

Section: Introductionmentioning

confidence: 99%

Investigation of Bradykinin metabolism in human and rat plasma in the presence of the dual ace/NEP inhibitors GW660511X and omapatrilat

Heudi

Ramírez-Molina

Marshall

et al. 2002

Journal of Peptide Science

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Several studies have suggested that the accumulation of bradykinin, or that of one its metabolites BK1-8, is involved in the occurrence of side effects such as AE associated with the use of various ACEi. In this work a novel approach combining HPLC-UV on-line with oaTOF-MS and ICPMS was applied to investigate in human and rat plasma the metabolism of labelled BK (79/81 Br-Phe5) BrBK in the presence of two new dual ACE/NEP inhibitors (GW660511X and omapatrilat) currently under clinical trial. In human plasma the BrBK half-life values in the absence or in the presence of GW660511X (3.8 microM) or omapatrilat (32 nM) were 38.7 +/- 2.4, 51.2 +/- 4.7 and 114.7 +/- 9.3 min, respectively and BrBK was degraded into BrBK1-8, BrBK1-7, BrBK1-5 and Br-Phe. In the presence of inhibitors, however, the levels of these resultant metabolites were different. Unlike GW660511X, omapatrilat abolished the production of BrBK1-5 and BrBK1-7, suggesting a better ACE inhibition effect over GW660511X as no NEP activity was found. In addition the production of BrBK1-8 was enhanced in the presence of these inhibitors with a greater accumulation being observed with omapatrilat. The production of Br-Phe5 was reduced with GW660511X while no significant change was observed with omapatrilat after 4 h of incubation. In rat plasma the BrBK half-life values in the absence or in the presence of GW660511X (530 nM) or omapatrilat (50 nM) were 9.31 +/- 1.7, 22.06 +/- 3.1 and 25.3 +/- 1.7 min, respectively and BrBK was degraded into BrBK1-8, BrBK1-7, BrBK1-5 and Br-Phe5 plus BrBK2-9, BrBK4-8 and BrBK2-8 metabolites not found in human plasma. GW660511X and omapatrilat reduced the production of BrBK1-5 and BrBK1-7 with more effect being observed with omapatrilat. GW660511X and omapatrilat increased the production of both BrBK1-8 and Br-Phe5 but not that of BrBK4-8 and BrBK2-8. This study shows that the potency of GW660511X in comparison with omapatrilat is more than 100-fold lower in human, but less than 10-fold lower in rat plasma, suggesting that rat may not be a suitable in vivo model for the evaluation of ACE/NEP inhibition in relation to effects in humans.

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“…The results of a number of authors show that when intrapleural injection of des-Arg9-BK occurs with a temporary dependence of migration of the inflammatory cell, characterized mainly by the use of mononuclear cells and neutrophil cells [5].…”

Section: амурский медицинский журнал №3 (19) 2017mentioning

confidence: 99%

Morphological examination of mesenterium of the intestine tenue during experimental hypogravitation

Seliverstov¹,

Zinoviev²,

Shakalo³

et al. 2017

AMJ

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Амурский медицинский журнал №3 (19) 2017Cellular reactions were studied in mycobacteria in pleurisy in mice. The pleurisy caused two peak cellular influx at 1 and 15 days after infection. In the first hour, macrophages were found. Neutrophils appeared after 2 hours of infection and reached a maximum of 4 hours with a high dose of infection. This was accompanied by a large accumulation of eosinophils during the inflammatory cell reaction to M. Bocis M. Bovis in the pleural cavity of the mouse than to other known eosinophilia inducers: IL-5, PAF-acether. Mycobacterial and mouse susceptibility determine the early dynamics of changes in granulocytes [6].Aluminum lactate, introduced to experimental rats, produced skeletal necrosis of the muscle of the diaphragm and abdominal wall. Ultrastructural studies of the diaphragm showed inoculation covering the collagen fibers that connect near the basal plate of the muscle, and limited within the phagocytes [2].The results of a number of authors show that when intrapleural injection of des-Arg9-BK occurs with a temporary dependence of migration of the inflammatory cell, characterized mainly by the use of mononuclear cells and neutrophil cells [5].Pleural reaction to damage is a multifactorial process that can result in the development of fibrosis with obliteration of the pleural cavity, or it can restore the pleura to its normal state. Today, we do not have adequate models of chronic inflammation and all that can be achieved with a set of available tests is to predetermine and evaluate the activity of new compounds, but not their side effects. Amur State Medical Academy, Blagoveshchensk, RussiaMorphological examination of mesenterium of the intestine tenue during experimental hypogravitation.Key words: mesenterium, experimental hypogravitation Summary. Morphological approaches to the study of the microcirculatory bed of the mesentery of experimental animals have been developed in experimental hypogravity of the organism. It has been established that in the case of antiorthostic hanging of rats, conditions are created for the redistribution of blood, which leads to the accumulation of blood in the veins of the mesentery.Introduction. Biomicroscopy of the mesenterium is a fundamental way of studying microhemocirculation. Its relevance is indicated by the need to evaluate the obvious effects of gravity on blood circulation, during overload and weightlessness of the body [2]. The aim of the study was to develop morphological approaches to the study of the microcirculatory bed of mesentery of experimental animals under experimental hypogravity of the organism.Methods of research. The object of the study was white male rats weighing 240 g. We identified two groups of animals. The first control group is 9 animals. The second group of animals-8 animals underwent experimental influence of hypogravity according to the classical Novikov-Il'in method [1]. The obtained film preparation of mesenterium intestine tenue after fixing in formalin the color of the mesentery with an aqueous sol...

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Analysis of the mechanisms involved in the inflammatory response induced by des-Arg9-bradykinin in the rat pleural cavity

Abstract: These findings suggest that inflammatory responses caused by the B1 agonist des-Arg9-BK in the rat pleural cavity are mediated by a receptor-independent mechanism, being largely dependent on the activation of resident mast cells and release of histamine and/or serotonin.

Cited by 8 publications

References 27 publications

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

Interactions between bradykinin (BK) and cell adhesion molecule (CAM) expression in peptidoglycan‐polysaccharide (PG‐PS)‐induced arthritis

Investigation of Bradykinin metabolism in human and rat plasma in the presence of the dual ace/NEP inhibitors GW660511X and omapatrilat

Morphological examination of mesenterium of the intestine tenue during experimental hypogravitation

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